Proton-Coupled Electron Transfer at the Surface of Polyoxovanadate-Alkoxide Clusters

Conspectus Proton-coupled electron transfer (PCET) is a fundamental process involved in all areas of chemistry, with relevance to biological transformations, catalysis, and emergent energy storage and conversion technologies. Early observations of PCET were reported by Meyer and co-workers in 1981 while investigating the proton dependence of reduction of a molecular ruthenium oxo complex. Since that time, this conceptual framework has grown to encompass an enormous scope of charge transfer and compensation reactions. In this Account, we will discuss ongoing efforts in the Matson Laboratory to understand the fundamental thermodynamics and kinetics of PCET processes at the surface of a series of Lindqvist-type polyoxovanadate clusters. This project aims to provide atomistic resolution of net H atom uptake and transfer at the surfaces of transition-metal oxide materials. First, we discuss our efforts aimed at understanding PCET at metal oxide surfaces using the Lindqvist-type polyoxovanadate-alkoxide (POV-alkoxide) cluster [nBu4N]2[V6O13(TRIOLNO2)2]. These clusters reversibly bind H atom equivalents at bridging oxide sites, mirroring the proposed uptake and release of e–/H+ pairs at transition-metal oxide surfaces. Summarized results include the measurement of bond dissociation free energies of surface hydroxide moieties (BDFE(O–H)) as well as mechanistic analyses that verify concerted proton electron transfer as the operative pathway for PCET at the surface of POV-alkoxide clusters. Next, we discuss net proton and H atom uptake at the surface of reduced variants of the Lindqvist-type POV-alkoxide cluster, [V6O7(OR)12]n (R = Me, Et; n = −2, −1, 0, + 1). In the case of these low-valent POV-alkoxide clusters, nucleophilic bridging sites are kinetically inhibited by functionalization of the cluster surface with organic ligands. This molecular modification enables site-selectivity in proton and H atom uptake to terminal oxide sites. The impact of reaction site and cluster electronics on reaction driving force of PCET is explored, with core electron density playing a critical role in dictating thermodynamics of H atom uptake and transfer. Additional work described here contrasts the kinetics of PCET at terminal oxide sites to the reactivity observed at bridging oxides in POV-alkoxide clusters. Overall, this Account summarizes our foundational knowledge regarding the assessment of PCET reactivity at the surfaces of molecular metal oxides. Drawing analogies between POV-alkoxide clusters and nanoscopic metal oxide materials provide design principles for the advancement of materials applications with atomic precision. These complexes are additionally highlighted as tunable redox mediators in their own right; our studies demonstrate how cluster surface reactivities can be optimized by modifying electronic structure and surface functionalities.

15768. 2 4 This publication examines the thermochemistry and mechanism of the reduction of terminal oxido moieties of polyoxovanadate-alkoxides by proton-coupled electron transfer.

■ INTRODUCTION
The rich electrochemical properties of transition-metal oxides have positioned these materials as valuable mediators in emergent energy-related technologies (e.g., fuel cells, 5 optoelectronic devices, 6 photo/electrochemical catalysts 7 ). In all these applications, a defining feature of active materials is their ability to accept and transfer H atom equivalents (i.e., proton/electron pairs) via proton-coupled electron transfer (PCET). The mechanism(s) of these processes have been interrogated by both empirical and computational methods, providing evidence for both concerted proton-electron transfer (CPET) and electron transfer-proton transfer (ET-PT) pathways (Scheme 1). However, further progress in performance optimization via materials design requires an improved understanding of thermal and kinetic considerations that dictate the reactivity of H atom equivalents at the surface of transition-metal oxides. PCET reactivity mediated by transition-metal oxides is governed by thermodynamics, where the difference in energies of bonds broken and formed influences reaction equilibria. 8−10 Further progress in predicting the thermochemistry of O−H bond formation and cleavage at metal oxide surfaces requires improved atomistic insight into the nature of reactive sites, and the role local structures play in influencing bond dissociation free energy (BDFE(O−H)) values. 11 To this end, valuable information has been gained from theoretical investigations. Several reports have outlined the optimized structures of H atoms bound to oxides, providing insight into preferred binding sites at various H atom doping levels. 12 Direct experimental insight into the reactivity of H atom equivalents at metal oxide surfaces has been hampered by the complexity of bulk transition-metal oxides. Indeed, the extended structure of these materials results in competing H atom intercalation 13 and the presence of defect sites that alter mechanisms of PCET postulated for the pristine assembly. 14 To circumvent these challenges, the study of molecular models has become an attractive route to both understand reactivity and bonding as well as uncover design criteria for subsequent material development. 15,16 Polyoxometalates (POMs) stand out as a particularly intriguing family of compounds for understanding PCET at metal oxide surfaces. 17 Composed of multiple transition-metal centers linked together through bridging oxygen atoms, these molecular metal oxides exist on the continuum between small molecules and extended solids. Of relevance to PCET in metal oxide materials, POMs feature reduction potentials that are sensitive to acid concentration, indicating net H atom uptake under reducing conditions. 2,18,19 Notably, the molecular structure of POMS limits all reactivity with protons to the surface of the complex, poising POMs to serve as efficient PCET mediators by eliminating kinetic barriers associated with lattice intercalation of H atoms.
A distinct subclass of POMs is the Lindqvist-type polyoxovanadate-alkoxide (POV-alkoxide) cluster: (Figure 1). These hexavanadate assemblies differ from canonical POMs in that the high charge density of the small [V 6 O 19 ] −8 core destabilizes this structure in the absence of bridging ligands. 20 Decreasing the charge of oxide linkers by organofunctionalization stabilizes composite V centers in a variety of oxidation states (e.g., V III , V IV , V V ), facilitating access to a range of core electronic structures. 21 Scheme 1. A Generalized Square Scheme Depicting Individual Electron and Proton Transfer Events That Make up a PCET reaction, with Their Respective Thermochemical Values (i.e. E 0 and pK a ) a a Concerted electron/proton transfer from XH is represented by the reaction on the diagonal. The thermochemistry of X−H bond scission is defined throughout our work by the BDFE of the X−H bond. Figure 1. Net H atom uptake at polyoxovanadate-alkoxide surfaces described in this work (top), which provide thermodynamic and kinetic insights into similar reactivity at metal oxide surfaces (bottom). While a variety of other H atom uptake sites are possible in materials, we highlight the binding modes for which we have generated cluster analogues.
Additionally, the diverse range of ligands reported in POValkoxide structures provide opportunities to investigate the role surface ligands play in influencing the physicochemical properties of nanoscopic metal oxides. 21 This Account is a summation of the work our group has performed over the past 4 years building an understanding of PCET at the surface of POV-alkoxide clusters. Our work with high-and low-valent derivatives of these hexavanadate assemblies has allowed our team to elucidate factors that influence net H atom uptake and transfer at bridging and terminal-oxide sites. [1][2][3][4]16,22,23 Efforts described here outline various approaches for BDFE(O−H) determination in molecular cluster complexes. 1,2,4,23 We also summarize a series of thermodynamic and kinetic investigations that reveal details about the mechanism of PCET at metal oxide surfaces, with particular attention to the role oxide position plays in dictating rate and activation parameters of net H atom uptake. 1,2,4,23 Our group's approach to probing and comparing the thermal and kinetic factors that dictate PCET at POV-alkoxides provides atomistic insights into similar reactivity in bulk and nanocrystalline material surfaces. More importantly, this work has laid a foundation for the development of a unique class of efficient catalysts for PCET-mediated small molecule transformations.

PCET at Bridging Oxide Ligands in Polyoxovanadates
The interaction of reduced POMs with protons has been recognized for decades, noted most clearly in the substantial differences in electrochemical profiles of the metal oxide assemblies in neutral and acidic environments. In the absence of protons, most POMs exhibit 1e − reduction events. Addition of acid results in anodic shifts of these electrochemical processes; in some cases, individual redox processes appear to merge into multielectron/multiproton transfer events. To date, the majority of work has focused on leveraging multielectron reactivity in POMs for applications in energy storage devices. 24 The primary focus on performative metrics has resulted in comparatively less work emphasizing an understanding of PCET reactivity at the surface of POMs.
A 2015 study by Sami and co-workers was the first example of the explicit determination of a BDFE(O−H) for a reduced POM. 25 The authors chose to investigate the divanadiumsubstituted polyoxotungsate cluster, [PV 2 W 10 O 40 ] −5 . The incorporation of vanadate ions into the tungsten assembly increases the basicity of the cluster surface, directing proton uptake to the bridging oxide moieties located between vanadium ions. Through the use of the Bordwell equation   1,2 In all examples, H atom uptake occurs at bridging oxido ligands. Our team opted to investigate the nitro-substituted variant of the POV-alkoxide cluster due to its modest reduction potential and improved crystallinity. 1 Comparable reactivity of V 6 O 13 −2 with H atom equivalents was observed, as outlined in Scheme 2. Formation of the reduced complexes was confirmed by electronic absorption spectroscopy and electrospray ionization mass spectrometry (ESI-MS). Additionally, structural character- −2 ) reduced complexes was possible via single crystal Xray diffraction.
At the outset of our studies, we sought to determine thermochemistry of proton and electron transfer to the parent POV-alkoxide cluster, V 6 O 13 −2 . Our original plan relied on our ability to measure individual electron transfer and proton transfer steps. While isolation of the reduced form of the POValkoxide cluster, [V 6 O 13 (TRIOL NO 2 ) 2 ] −3 , was straightforward, experiments targeting protonation of the Lindqvist ion proved difficult. These experimental challenges translated to significant barriers associated with the determination of BDFEs of the reduced variants of the POV-alkoxide cluster.
Initial studies to elucidate BDFE(O−H) avg of the bridging hydroxide moieties at the surface of V 6 O 13 −2 employed an elegant method reported by Dempsey and co-workers. 27 This strategy invokes the construction of a "Pourbaix" diagram adapted for nonaqueous systems. Reduction potentials of redox active complexes are measured in the presence of a series of organic acids with variable pK a values. Plotting the reduction Accounts of Chemical Research pubs.acs.org/accounts Article potential vs pK a of the added organic acid results in a diagram which allows thermochemical information describing proton and electron transfer to be obtained for unstable intermediates. The cyclic voltammogram (CV) of V 6 O 13 −2 was analyzed in the presence of organic acids with pK a values ranging from 9.1 to 39.5 ( Figure 2). Upon addition of organic acids with pK a values greater than 33, the electrochemical profile of V 6 O 13 −2 remained largely unchanged from that observed in the absence of protons, consisting of two one-electron reduction events. 2 In the presence of organic acids with pK a values ranging between 19 and 33, loss of reversibility and anodic shift of the second reduction event were observed. Under these experimental conditions, E 1/2 values for irreversible redox events were determined through evaluation of the second derivative of the CV. 2 In the case of CVs run of V 6 O 13 −2 in the presence of organic acids with pK a values <19, the two distinct oneelectron reduction events collapse into a single, two-electron redox process. The slope of ∼60 mV/pK a , calculated by linear regression for the portion of our potential-pK a diagram from pK a 9−19, indicates a 1:1 ratio of protons to electrons transferred which we can attribute the 2e − /2H + transfer between V 6 O 11 (OH) 2 −2 and V 6 O 13 −2 . The construction of a potential-pK a diagram allows for the approximation of the pK a values of protonated and reduced forms of . In Figure 2, the points where acidindependent redox events (horizontal lines) intersect aciddependent redox events (diagonal line) indicate the basicity of the cluster is sufficient to deprotonate the acid present in solution. This data shows that the reduced forms of V 6  Having experimentally determined the pK a and E 1/2 for , the BDFE of surface-bound H atoms was calculated to be 65.3 kcal mol −1 using the Bordwell equation (eq 1). The BDFE(O−H) avg value obtained describes the average free energy for the transfer of 2e-/2H + from During the collection of the data presented above, an alternative electrochemical method for the determination of BDFE(E−H) of substrates in nonaqueous systems was published by Mayer and co-workers (note that this methodology was adapted from a technique originally presented by Roberts and Bullock 28 ). 29 By measuring the open circuit potential (OCP) of any chemically reversible redox process at equilibrium over a range of concentrations, one can extrapolate the thermodynamics of E−H bond formation for the overall PCET reaction. The OCP can then be directly translated to BDFE(E−H) according to eq 2: where E o (X/XH) is equal to the open circuit potential for a 1:1 ratio of reduced and oxidized cluster and ΔG o is a constant related to the free energy required to homolytically cleave H 2 in a given solvent. The OCP analytical method was used by our research team to confirm the BDFE(O−H) avg of V 6 O 11 (OH) 2 −2 ( Figure 3). For these measurements, an electrochemical cell was prepared containing N,N-dimethylaniline/N,N-dimethylanilinium tetrafluoroborate (DMA/DMAH + ) buffer and supporting electrolyte in acetonitrile. The DMA/DMAH + buffer was selected based on its ability to facilitate the desired 2e − /2H + transfer to the cluster surface; the pK a value of DMAH + (11.5) corresponds to the region of potential-pK a diagram hypothesized to result in 2e − /2H + transfer.
A plot of the measured OCPs against the log of the ratio of concentration of V 6 O 11 (OH) 2 −2 and its oxidized counterpart V 6 O 13 −2 yields the expected Nernstian dependence for a 2e − / 2H + transfer (−0.037 ± .0033 V dec −1 ). When referenced

Accounts of Chemical Research
pubs.acs.org/accounts Article against the H + /H 2 couple, the OCP for a 1:1 ratio of reduced and oxidized cluster is 0.595 V (y-intercept in Figure 3).  The results summarized above confirm analogous BDFE-(O−H) avg values for V 6 O 11 (OH) 2 −2 through a variety of experimental techniques. While any one of these methods are reliable for the determination of thermochemical descriptors of PCET at POM surfaces, our group has found favor with the OCP analysis method. We have since applied OCP analysis to evaluate BDFE(O−H) avg of the most reduced variant of the series summarized in Scheme 2, V 6 O 7 (OH) 6 −2 (Figure 4). The OCP was measured for a series of solutions containing various ratios of V 6 O 7 (OH) 6 −2 and its oxidized counterpart, V 6 O 9 (OH) 4 −2 , along with supporting electrolyte and excess 1,1,3,3-tetramethylguanidine/1,1,3,3-tetramethylguanidinium tetrafluoroborate (pK a (TMG/TMGH + ) = 23.35 in acetonitrile). It is important to note the use of a different buffer in these OCP analyses; a weaker acid was selected due to the increased basicity of the reduced POV-alkoxide surface. 1 Results revealed a 2e − /2H + transfer from V 6 9 In this report, a 13 kcal mol −1 change in BDFE(O−H) avg for surface-bound H atoms on ceria was accomplished by tuning the ratio of Ce III /Ce IV in the material from 17.5 to 72.2%. This is a substantially greater change than the 0.6 kcal mol −1 predicted by the Nernst equation. Similarly, the 4 kcal mol −1 change in BDFE(O−H) avg observed between V 6 O 11 (OH) 2 −2 and V 6 O 7 (OH) 6 −2 is 5 times greater than predicted. This is reasonable considering the Robin and Day Class II delocalized electronic structure of the mixed-valent Lindqvist complexes along the 6e − /6H + reduction scheme, meaning electronic delocalization in the core is thermally limited. Partial charge localization in both systems results in deviations to M−O bond geometries (e.g., bond lengths and angles), resulting in nonidealized, chemically distinct surface sites which break the predicted Nernstian dependence of BDFE on electronic occupancy. 9 The

PCET at Terminal Oxides in Polyoxovanadates
While bridging oxide ligands have been shown to be integral to facilitating net H atom transfer reactions at the surface of POMs, 1,2,18 there is a lack of research probing similar phenomena at terminal oxides. 3,4,22,23 Accordingly, our research team has studied PCET in a series of reduced, Lindqvist-type POV-alkoxide clusters, [V 6 O 7 (OR) 12 ] n (R = Me, Et); saturation of bridging positions stabilizes a range of charge states as evident in CV (n = −2, −1, 0, +1; Figure 5). 32 Complete functionalization of the POV surface additionally serves to block the nucleophilic bridging sites of the cluster, directing PCET to surface V�O moieties.
Proton Uptake in POV-Alkoxide Clusters. Toward understanding PCET at organosaturated POV-alkoxide clusters, initial work probed the reactivity of the fully reduced cluster with protons. 3,22 Addition of 1 equiv of triethylammonium tetrafluoroborate to [V 6 O 7 (OEt) 12 ] −2 results in a 1:1 mixture of products, namely [V 6 O 7 (OEt) 12 ] −1 and [V 6 O 6 (MeCN)(OEt) 12 ] −1 . The ability to access an O atomdeficient POV-alkoxide (i.e., [V 6 O 6 (MeCN)(OEt) 12 ] −1 ) through the addition of acid is broadly reminiscent of the surface acid/base chemistry of bulk metal oxides ( Figure 6). 33 Protonation of a terminal M n �O moiety produces an unstable, M n −OH which may disproportionate to form M n+1 =O and M n−1 −OH 2 sites at the surface. We propose a similar mechanism is operative in the case of POV-alkoxide clusters; protonation of [V 6 (Figure 7). 24 Subsequently our team interrogated the dependence of cluster oxidation state on the basicity of the vanadium oxide assembly. 3 Toward this goal, we probed the reactivity of [V 6 O 7 (OMe) 12 ] −2 (V IV 6 ), [V 6 O 7 (OMe) 12 ] −1 (V IV 5 V V ) and    With these results in hand, a mechanism of defect formation via H atom uptake is proposed (Scheme 5). 36 A ratedetermining CPET step from H 2 Phen to [V 6 O 7 (OMe) 12 ] −1 results in formation of [V 6 O 6 (OH)(OMe) 12 ] −1 , followed by the rapid transfer of the second H atom equivalent from the organic reagent to generate [V 6 O 6 (OH 2 )(OMe) 12 ] −1 . When this reaction is conducted in MeCN, the aquo ligand is displaced, giving rise to the final product, [V 6 O 6 (MeCN)-(OMe) 12 ] −1 . We find that this reactivity curtails the disproportionation step that follows protonation of the terminal oxo, as the second N−H bond is expected to be significantly weaker, 8 providing driving force for the second H atom equivalent to be directly installed by the 1e − /1H + oxidized hydrophenazyl radical. This distinguishes the reactivity of the organic-saturated POV-alkoxides with H atom versus proton donors, as the ready availability of a second H atom equivalent curtails disproportionation of transiently formed terminal hydroxide-containing species.
As the oxidation state distribution of distal vanadium ions was observed to have a dramatic impact on the basicity of the cluster surface, we hypothesized that charge state of the assembly would influence the thermodynamics of H atom uptake.  (Figure 8). This series of results indicates that the

■ CONCLUSIONS AND OUTLOOK
In this Account, we have summarized our efforts to provide atomic insight into PCET reactivity at metal oxide surfaces using POV-alkoxide clusters. The work described predominantly focuses on the quantification of the free energy of O−H bonds formed at the surface of reduced vanadium oxide assemblies. Structural modifications to the POV-alkoxide precursor allow our research team to interrogate differences in thermodynamics of O−H bonds generated at terminal-and bridging-oxide sites, providing insight into the regioselectivity of net H atom uptake at transition-metal oxide surfaces. The bridging oxides of high-valent, Lindqvist-type POValkoxide clusters are able to store up to 6 proton/electron pairs at the surface of the assembly. Net H atom uptake and transfer occurs pairwise in these systems, with isolable forms of the reduced assembly differing by 2 H atom equivalents (e.g., Addition of H atom equivalents to the surface of the assembly results in reduction of V V =O moieties to V III −OH 2 . Mechanistic investigations reveal that net H atom uptake occurs via a series of CPET-type reactions. Our experiments reveal BDFE(O−H) values for purported hydroxide-substituted intermediates, [V 6 O 6 (OH)(OMe) 12 ] n , range between 60 and 66 kcal mol −1 ; with the lability of surface H atoms similarly correlated to the oxidation state distribution (i.e., core electron density) of vanadium ions.
Our investigations quantifying thermodynamic and kinetic properties of PCET in POV-alkoxide clusters at disparate oxido ligands provide a launch point for future mechanistic work. Our findings indicate comparable thermodynamic driving forces for H atom installation at these disparate sites, suggesting selectivity for a particular type of oxide moiety may be governed by kinetics of the relevant PCET reactions. Recent work has demonstrated the ability to modify PCET pathways for a given substrate through changes in molecular structure and reaction environment. 37 Such mechanistic changes can result in increased selectivity for small molecule activation. Ongoing investigations by our research team aim to develop an understanding of how modifications to the structure of the POV-alkoxide influence the mechanism of PCET at the surface of the cluster. Promising preliminary results show striking variations in kinetic isotope effects and activation parameters, indicating that fundamental concepts understood in discrete monometallic catalysts for net H atom transfer can also be leveraged to control the reactivity in multimetallic metal oxide assemblies.